Initial treatment involves supporting the person's breathing and providing oxygen.[7]Naloxone is then recommended among those who are not breathing to reverse the opioids effects.[7][3] Giving naloxone into the nose or as an injection into a muscle appears to be equally effective.[12] Among those who refuse to go to hospital following reversal, the risks of a poor outcome in the short term appear to be low.[12] Efforts to prevent deaths from overdose include improving access to naloxone and treatment for opioid dependence.[1]

Opioid use disorders resulted in 122,000 deaths globally in 2015, up from 18,000 deaths in 1990.[8][13] In the United States over 49,000 deaths involved opioids in 2017.[5] Of those about 20,000 involved prescription opioids and 16,000 involved heroin.[5] In 2017 opioid deaths represented more than 65% of all drug overdose related deaths in the United States.[5] The opioid epidemic is believed to be in part due to assurances in the 1990s by the pharmaceutical industry that prescription opioids were safe.[4]

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Because of their effect on the part of the brain that regulates breathing, Opioids can lead to the person not breathing (respiratory depression) during overdoses and therefore result in death.[1] Opiate overdose symptoms and signs can be referred to as the "opioid overdose triad": decreased level of consciousness, pinpoint pupils and respiratory depression. Other symptoms include seizures and muscle spasms. Sometimes a person experiencing an opiate overdose can lead to such a decreased level of consciousness that he or she won't even wake up to their name being called or being shaken by another person.

Prolonged hypoxia from respiratory depression can also lead to detrimental damage to the brain and spinal cord and can leave the person unable to walk or function normally, even if treatment with naloxone is given.

Alcohol also causes respiratory depression and therefore when taken with opioids can increase the risk of respiratory depression and death.[1]

In young children, opioid overdose may not be apparent right away. This is due to absorption, distribution, and metabolism differences between young children and adults, and the higher amount of opioid ingestion per kilogram of body weight.[3]

Risk factors for opioid overdose include opioid dependence, injecting opioids, using high doses of opioids, and use together with alcohol, benzodiazepines, or cocaine.[1][5] The risk is particularly high following detoxification.[1] Dependence on prescription opioids can occur from their use to treat chronic pain.[1] In young children an overdose is usually due to opioids that are intended for their parents, older siblings, or grandparents.[15] In mothers who take codeine during breastfeeding, opioid overdoses have occurred in their baby.[16] Codeine is therefore not recommended in those who are breastfeeding.[16]

Opioid overdoses are often associated with benzodiazepines or alcohol use.[17][18] Other CNS depressants, muscle relaxers, pain relievers, anti-convulsants, anxiolytics, treatment drugs of a psychoactive or epileptic variety or any other such drug with its active function meant to calm or mitigate neuronal signaling (barbiturates, etc.) can additionally cause a worsened condition with less likelihood of recovery cumulative to each added drug. This includes drugs less immediately classed to a slowing of the metabolism such as with GABAergics like GHB or glutamatergic antagonists like PCP or ketamine.

The top line represents the yearly number of benzodiazepine deaths that involved opioids in the US. The bottom line represents benzodiazepine deaths that did not involve opioids.[5]

Opioid involvement in cocaine overdose deaths. The yellow line (the top line in later years) represents the number of yearly cocaine deaths that also involved opioids.[5]

Opioids are metabolized by the liver before they are excreted in the urine and each opioid may be metabolized by different cytochrome P450 enzymes.[3] Polymorphisms in CYP superfamily of genes vary by individual and can account for differences in therapeutic response to drugs.[19] This biotransformation of opioids by the liver can either lead to the inactivation or activation of the drug.[20] For example, methadone is converted primarily by CYP3A4 liver enzyme to an inactive metabolite.[20] In contrast, codeine is an initially inactive prodrug that is metabolized by CYP2D6 to its active form morphine to exert its analgesic effects.[21] An individual who has a poor metabolizer phenotype of CYP2D6 may experience weak analgesic effects with codeine while someone who has the ultra-rapid metabolizer phenotype would experience greater side effects.[21]

Permanent brain damage may occur due to cerebral hypoxia or opioid-induced neurotoxicity.[2][22] Opioids inhibit the medulla's chemoreceptors through the mu and delta receptors.[23] Opioids bind to receptors that are part of the endogenous opioid system as well as other central nervous neurotransmitter systems, binding to excitatory neurotransmitters like dopamine or glutamate, or inhibitory neurotransmitters like GABA. The main excitatory chemoreceptor, glutamate, and main inhibitory chemoreceptor, GABA, are the main neurotransmitters that control respiration.[24] Because of its fatal consequences, opioid induced respiratory depression is one of the major limiting factors of its analgesic effects.[25] Opioids vary in the rate of metabolism amongst individuals. The rate of metabolism of opiates vary due to genetic factors while tolerance of the opiates can determine risk.[26]

Opioid overdoses can often be prevented.[27][28] Clear protocols for staff at emergency departments and urgent care centers can reduce opioid prescriptions for individuals presenting in these settings who engage in drug seeking behaviors or who have a history of substance abuse.[29] Drug seeking behaviors include but are not limited to obsessiveness or impatience when it comes to attaining medications, seeking multiple pain adjunct medications, and inconsistent physiological presentation.[30] A limited amount of evidence suggests opioid therapy with extended-release or long-acting formulations may increase the risk of an unintentional overdose compared to shorter-acting agents.[31] Routinely screening using tools such as the CAGE-AID and the Drug Abuse Screening Test (DAST-10) in adults and the CRAFFT in those aged 14–18 years is recommended.[27] Other “drug seeking” behaviors and physical indications of drug use should be used as clues to perform formal screenings.[27]

There are several medication-assisted treatments available for people with opioid use disorder or opioid dependence, who are at higher risk for opioid overdose.[32][33] The selection of treatment depends on various factors, such as a person's preference, accessibility, and history of treatment.[33] Examples of medication-assisted treatments are buprenorphine (with or without naloxone), naltrexone, and methadone.[34][35] Peer support groups have tentative evidence of benefit.[36] There is also some evidence indicating benefits in community-based overdose education and naloxone distribution programs.[37] Buprenorphine and methadone can help decrease drug cravings.[33] Combining pharmacologic treatments with behavioral therapy, such as support or recovery groups, can increase likelihood of overcoming addiction and reduce the risk of an opioid overdose.

Individuals diagnosed with opioid dependence should be prescribed naloxone to prevent overdose and/or should be directed to one of the many intervention/treatment options available, such as needle exchange programs and treatment centers.[27][28] Brief motivational interviewing can also be performed and has been shown to improve people's motivation to change their behavior.[27][38] Despite these opportunities, the dissemination of prevention interventions in the US has been hampered by the lack of coordination and sluggish federal government response.[28]

In people who have overdosed on opioids, basic life support and naloxone are recommended as soon as possible. Naloxone is effective at reversing the cause, rather than just the symptoms, of an opioid overdose.[39] Compared to adults, children often need larger doses of naloxone per kilogram of body weight.[3]

Programs to provide drug users and their caregivers with naloxone are recommended.[40] In the United States, as of 2014, more than 25,000 overdoses have been reversed.[41][42] Programs training police and fire personnel in opioid overdose response using naloxone have also shown promise.[43]

Of the more than 72,000 overdose deaths in the US in 2017, opioids were involved in over 49,000.[5] This is an increase from 2016 where over 64,000 died from drug overdose, and opioids were involved in over 42,000.[44] In 2016, the five states with the highest rates of death due to drug overdose were West Virginia (52.0 per 100,000), Ohio (39.1 per 100,000), New Hampshire (39.0 per 100,000), Pennsylvania (37.9 per 100,000) and Kentucky (33.5 per 100,000).[45][44]

Concerning the 2017 data in the charts below deaths from the various drugs add up to more than 72,000 because multiple drugs are involved in many of the deaths.[45]

US yearly overdose deaths, and the drugs involved. Among the more than 72,000 deaths estimated in 2017, the sharpest increase occurred among deaths related to fentanyl and synthetic opioids (more than 29,000 deaths).[5]

Charts of deaths involving specific opioids and classes of opioids

US yearly deaths from all opioid drugs. Included in this number are opioid analgesics, along with heroin and illicit synthetic opioids.[5]

The Substance Abuse and Mental Health Services Administration hosts an annual health observance known as National Prevention Week. Every third week of May, they encourage communities across the country unite to share stories about positive mental and behavioral health and the importance of implementing prevention methods.[46] They also sponsors Recovery Month every September. Recovery Month aims to raise awareness about mental and substance use disorders and to honor individuals who recover, promoting the positive message that prevention works and that treatment is effective.[47]